tbuckley/cabot-search huggingface dataset:
Safety of upadacitinib in moderate-to-severe atopic dermatitis: An integrated analysis of phase 3 studies
Authors: Emma Guttman-Yassky, Jacob P. Thyssen, Jonathan I. Silverberg, Kim A. Papp, Amy S. Paller, Stephan Weidinger, H. Chih-ho Hong, Barbara Hendrickson, Deanne Dilley, Allan R. Tenorio, Barry Ladizinski, Alvina D. Chu, John Liu, Alan D. Irvine
Journal: Journal of Allergy and Clinical Immunology (2022)

Upadacitinib is a selective reversible Janus kinase (JAK) inhibitor with established efficacy in moderate-to-severe atopic dermatitis (AD).We evaluated the safety of upadacitinib in patients with moderate-to-severe AD.Integrated safety data from the 16-week placebo-controlled periods of 1 phase 2b and 3 ongoing phase 3 studies (16 weeks) and longer-term safety data from patients receiving upadacitinib during the blinded extension periods of the three phase 3 studies were analyzed (all upadacitinib exposure). Treatment-emergent adverse events (TEAEs) were presented as exposure-adjusted rates per 100 patient-years (PY).Safety results were similar between the 16-week and all upadacitinib exposure groups. The latter group included 2485 patients (333 adolescents), receiving upadacitinib 15 mg (n = 1239) or 30 mg (n = 1246) for a mean duration of approximately 1 year. Upadacitinib was well tolerated by both adults and adolescents. TEAEs and discontinuation due to AEs were reported more frequently in patients receiving 30 mg upadacitinib (respectively, 311.9 and 5.7 events per 100 PY) versus 15 mg (respectively, 274.6 and 4.4 events per 100 PY). Serious adverse event rates (15/30 mg, 7.1/7.7 events per 100 PY) were similar in both groups. Acne was the most frequently reported adverse event (15/30 mg, 13.3/20.2 events per 100 PY). Serious infection rates were similar across treatment groups. Adjudicated major adverse cardiovascular event and venous thromboembolic event rates were ≤0.1 events per 100 PY. Rates of malignant neoplasms were within the expected range for the general population.Upadacitinib was well tolerated, and no new important safety risks were observed among adults and adolescents with moderate-to-severe AD treated for approximately 1 year compared to the known safety profile of upadacitinib.
Re: Isamu Tachibana, Sean Q. Kern, Antoin Douglawi, et al. Primary Retroperitoneal Lymph Node Dissection for Patients with Pathologic Stage II Nonseminomatous Germ Cell Tumor—N1, N2, and N3 Disease: Is Adjuvant Chemotherapy Necessary? J Clin Oncol. In press. https://doi.org/10.1200/JCO.22.00118
Authors: Alireza Ghoreifi, Hooman Djaladat
Journal: European Urology (2022)
Re: Bernadett Szabados, Mark Kockx, Zoe June Assaf, et al. Final Results of Neoadjuvant Atezolizumab in Cisplatin-ineligible Patients with Muscle-invasive Urothelial Cancer of the Bladder. Eur Urol 2022;82:212–22
Authors: Zihan Zhao, Hongqian Guo, Rong Yang
Journal: European Urology (2022)
Reply to Alireza Ghoreifi and Hooman Djaladat’s Letter to the Editor re: Isamu Tachibana, Sean Q. Kern, Antoin Douglawi, et al. Primary Retroperitoneal Lymph Node Dissection for Patients with Pathologic Stage II Nonseminomatous Germ Cell Tumor—N1, N2, and N3 Disease: Is Adjuvant Chemotherapy Necessary? J Clin Oncol. In press. https://doi.org/10.1200/JCO.22.00118
Authors: Isamu Tachibana, Sean Q. Kern, Antoin Douglawi, Yan Tong, Mohammad Mahmoud, Timothy A. Masterson, Nabil Adra, Richard S. Foster, Lawrence H. Einhorn, Clint Cary
Journal: European Urology (2022)
Randomized, Controlled Trial of a Digital Behavioral Therapeutic Application to Improve Glycemic Control in Adults With Type 2 Diabetes
Authors: Judith Hsia, Nicole L. Guthrie, Paul Lupinacci, Ananda Gubbi, Douglas Denham, Mark A. Berman, Marc P. Bonaca
Journal: Diabetes Care (2022)

OBJECTIVE To evaluate the efficacy and safety of a digital therapeutic application (app) delivering cognitive behavioral therapy (CBT) designed to improve glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Adults with type 2 diabetes and an HbA1c of 7 to &amp;lt;11% were randomly assigned to receive access to a digital therapeutic app delivering CBT (BT-001) or a control app, both on top of standard of care management. CBT is an established form of psychological treatment that endeavors to identify and change unhelpful thinking patterns. The primary study end point was treatment group difference in mean HbA1c change from baseline to 90 days. RESULTS Among 669 randomly assigned subjects who completed app onboarding, the mean age was 58 years, BMI 35 kg/m2, 54% were female, 28% Black, and 16% Latino. Baseline HbA1c was 8.2 and 8.1% in the BT-001 and control groups, respectively. After 90 days of app access, change in HbA1c was −0.28% (95% CI −0.41, −0.15) in the BT-001 group and +0.11% (95% CI −0.02, 0.23) in the control group (treatment group difference 0.39%; P &amp;lt; 0.0001). HbA1c reduction paralleled exposure to the therapeutic intervention, assessed as the number of modules completed on the app (P for trend &amp;lt;0.0001). No adverse events in either group were attributed to app use and no adverse device effects reported. CONCLUSIONS Patients randomly assigned to the BT-001 arm relative to the control arm had significantly lower HbA1c at 90 days. The digital therapeutic may provide a scalable treatment option for patients with type 2 diabetes.
Molecular and Developmental Signatures of Genital Size Macro-Evolution in Bugs
Authors: Bruno C Genevcius, Denis C Calandriello, Tatiana T Torres
Journal: Molecular Biology and Evolution (2022)

Abstract Our understanding of the genetic architecture of phenotypic traits has experienced drastic growth over the last years. Nevertheless, the majority of studies associating genotypes and phenotypes have been conducted at the ontogenetic level. Thus, we still have an elusive knowledge of how these genetic-developmental architectures evolve themselves and how their evolution is mirrored in the phenotypic change across evolutionary time. We tackle this gap by reconstructing the evolution of male genital size, one of the most complex traits in insects, together with its underlying genetic architecture. Using the order Hemiptera as a model, spanning over 350 million years of evolution, we estimate the correlation between genitalia and three features: development rate, body size, and rates of DNA substitution in 68 genes associated with genital development. We demonstrate that genital size macro-evolution has been largely dependent on body size and weakly influenced by development rate and phylogenetic history. We further revealed significant correlations between mutation rates and genital size for 19 genes. Interestingly, these genes have diverse functions and participate in distinct signaling pathways, suggesting that genital size is a complex trait whose fast evolution has been enabled by molecular changes associated with diverse morphogenetic processes. Our data further demonstrate that the majority of DNA evolution correlated with the genitalia has been shaped by negative selection or neutral evolution. Thus, in terms of sequence evolution, changes in genital size are predominantly facilitated by relaxation of constraints rather than positive selection, possibly due to the high pleiotropic nature of the morphogenetic genes.
sstar: A Python Package for Detecting Archaic Introgression from Population Genetic Data with <i>S</i>*
Authors: Xin Huang, Patricia Kruisz, Martin Kuhlwilm
Journal: Molecular Biology and Evolution (2022)

S* is a widely used statistic for detecting archaic admixture from population genetic data. Previous studies used freezing-archer to apply S*, which is only directly applicable to the specific case of Neanderthal and Denisovan introgression in Papuans. Here, we implemented sstar for a more general purpose. Compared with several tools, including SPrime, SkovHMM, and ArchaicSeeker2.0, for detecting introgressed fragments with simulations, our results suggest that sstar is robust to differences in demographic models, including ghost introgression and two-source introgression. We believe sstar will be a useful tool for detecting introgressed fragments in various scenarios and in non-human species.
Efficacy of gene delivery to the brain using AAV and ultrasound depends on serotypes and brain areas
Authors: Rikke Hahn Kofoed, Chinaza Lilian Dibia, Kate Noseworthy, Kristiana Xhima, Nathalie Vacaresse, Kullervo Hynynen, Isabelle Aubert
Journal: Journal of Controlled Release (2022)

Focused ultrasound combined with intravenously injected microbubbles (FUS) is known to non-invasively, locally, and transiently increase the permeability of the blood-brain barrier (BBB). A promising approach for non-invasive gene delivery to the brain is to administer recombinant adeno-associated viruses (AAVs) intravenously and allow them to cross the BBB at precise FUS-targeted brain regions. FUS-AAV delivery has been achieved in animal models; however, the key elements influencing, guiding, and monitoring the success of FUS-AAV delivery to the brain remain largely unknown. We systematically compared the ability of AAV1, AAV2, AAV5, AAV8, AAV9, and AAVrg to enter four specific brain regions and transduce two main cell types: neurons and astrocytes. Our results demonstrate that the AAV serotype, the extent of FUS-induced BBB permeability, and the intrinsic properties of the targeted brain tissue influence the observed biodistribution, diffusion and transduction of AAV to cells of the cerebrovasculature and brain parenchyma. Non-invasive contrast-enhanced MR imaging was found to predict the efficacy of FUS-AAV delivery. Notably, we also found that AAVs with high biodistribution to peripheral organs result in low gene delivery to the brain when combined with FUS. Gene delivery by AAV1, AAV2, AAV5, AAV8 and AAV9 was highly and selectively localized to FUS-targeted brain areas. To obtain non-invasive gene delivery to multiple brain regions with one area of FUS-BBB modulation, we combined a modified AAV2 vector harboring enhanced retrograde transport properties (AAVrg) with FUS-mediated brain delivery. This allowed for gene delivery from the FUS-targeted site to multiple connected brain regions. This study demonstrates that MR imaging can be used as a non-invasive indication of AAV delivery to the brain, and that the properties of AAV serotypes influence the efficacy of gene delivery to the brain with FUS. AAVs that have minimal peripheral biodistribution are ideal candidates for enhanced, and perhaps exclusive with future serotypes, delivery to the brain with FUS. The characterization of parameters influencing FUS-AAV delivery to the brain are critical to the design of safe and efficient gene therapies, from preclinical studies to future clinical applications.
An Ancient Respiratory System in the Widespread Sedimentary Archaea Thermoprofundales
Authors: Xinxu Zhang, Yuhan Huang, Yang Liu, Wei Xu, Jie Pan, Xiaowei Zheng, Huan Du, Cuijing Zhang, Zhongyi Lu, Dayu Zou, Zongbao Liu, Mingwei Cai, Jinbo Xiong, Yaxin Zhu, Zhiyang Dong, Hongchen Jiang, Hailiang Dong, Juquan Jiang, Zhuhua Luo, Li Huang, Meng Li
Journal: Molecular Biology and Evolution (2022)

Thermoprofundales, formerly Marine Benthic Group D (MBG-D), is a ubiquitous archaeal lineage found in sedimentary environments worldwide. However, its taxonomic classification, metabolic pathways, and evolutionary history are largely unexplored because of its uncultivability and limited number of sequenced genomes. In this study, phylogenomic analysis and average amino acid identity values of a collection of 146 Thermoprofundales genomes revealed five Thermoprofundales subgroups (A-E) with distinct habitat preferences. Most of the microorganisms from Subgroups B and D were thermophiles inhabiting hydrothermal vents and hot spring sediments, whereas those from Subgroup E were adapted to surface environments where sunlight is available. H2 production may be featured in Thermoprofundales as evidenced by a gene cluster encoding the ancient membrane-bound hydrogenase (MBH) complex. Interestingly, a unique structure separating the MBH gene cluster into two modular units was observed exclusively in the genomes of Subgroup E, which included a peripheral arm encoding the [NiFe] hydrogenase domain and a membrane arm encoding the Na+/H+ antiporter domain. These two modular structures were confirmed to function independently by detecting the H2-evolving activity in vitro and salt tolerance to 0.2 M NaCl in vivo, respectively. The peripheral arm of Subgroup E resembles the proposed common ancestral respiratory complex of modern respiratory systems, which plays a key role in the early evolution of life. In addition, molecular dating analysis revealed that Thermoprofundales is an early emerging archaeal lineage among the extant MBH-containing microorganisms, indicating new insights into the evolution of this ubiquitous archaea lineage.
Profile of Women Practicing Breast Self-examination
Authors: Susan E. Bennett
Journal: JAMA (1983)

The monthly practice of breast self-examination (BSE) can result in the early diagnosis of breast cancer. To explore factors that influence women's habits in the practice of BSE, we interviewed 616 women using an interactive computer program. We found that these women were more likely to practice BSE on a frequent basis if they were living with their sexual partner, had been shown how to perform BSE, and were confident in their examination technique. Women with a maternal history of breast disease were also more likely to practice monthly BSE. Unlike past reports that women with formal education beyond high school practice BSE more frequently than lesseducated women, our study showed no association between monthly BSE practice and formal education. Contrary to our hypothesis that BSE practice was associated with the practice of other preventive health activities, our study did not demonstrate such a relationship. These findings suggest that demonstrating BSE at the periodic health examination may help increase the number of women practicing BSE on a frequent basis. (<i>JAMA</i>1983;249:488-491)
Human leukocyte antigen A1-B8-DR3-DQ2-DPB1*0401 extended haplotype in autoimmune hepatitis
Authors: Koji Manabe, Peter T. Donaldson, James A. Underhill, Derek G. Doherty, Giorgina Mieli-Vergani, Ian G. McFarlane, Adrian L. W. F. Eddleston, Roger Williams
Journal: Hepatology (1993)

Genetic susceptibility to autoimmune hepatitis is associated with the human leukocyte antigen haplotype A1-B8-DR3 and DR4. To date, only one study in Japan has considered the human leukocyte antigen DP locus in this disease, and no studies have been reported in whites. In this study we used a series of sequencespecific oligonucleotide probes to determine human leukocyte antigen DPB1 genotypes in 101 unrelated white northern European patients and 105 racially and geographically matched controls. The aims of the study were twofold: first, to determine the degree of DPBencoded susceptibility to autoimmune hepatitis, and, second, to establish whether susceptibility can be extended to include human leukocyte antigen DPB. None of 17 DPB1 alleles was significantly associated with the susceptibility to autoimmune hepatitis. Although one particular seven-locus haplotype AlB8-DRB3*010-DRB1*0301-DQA1*0501-DQB1*02001-DPB1*0401 was significantly associated with the disease (27% vs. 7%, relative risk = 5.14, p &lt; 0.0005), the association with this haplotype was weaker than that for the six-locus haplotype excluding DPB (40% vs. 11%, RR = 5.52, p &lt; 0.0005). When the patients first seen at ages younger than 16 yr (pediatric patients) were considered separately, the greatest relative risk was for the seven-locus haplotype (41% vs. 7%; relative risk = 9.60, p &lt; 0.0005). The results of this study further confirm that major histocompatibility complex-encoded susceptibility to autoimmune hepatitis is located at or close to the human leukocyte antigen DR locus; however, the A1-B8-DR3-DQ2-DPB1*0401 extended haplotype may be important in determining the age of onset and severity of disease. (HEPATOLOGY 1993;18:1334-1337.)
Infection of Feline Embryo Adherent Cells With Feline Leukemia Virus: Feline Oncornavirus-Associated Cell Membrane Antigen Expression and Morphologic Transformation&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Journal: JNCI Journal of the National Cancer Institute (1981)

Feline embryo adherent cells were infected with the Rickard or Kawakami-Theilen strains of feline leukemia virus (FeLV) and examined for feline oncornavirus-associated cell membrane antigen (FOCMA), viral group-specific antigen (gsa) production, and in vitro evidence of transformation. As early as 10 days after infection. when more than half of the infected cells were gsa positive. FOCMA was detected on 5–10 percent of the cells. Transitory morphologic alterations (epithelioid appearance and rounding) were first noted in most cultures around 20–30 days post infection. At this time, approximately 50% of the cells in infected cultures expressed FOCMA. Morphologic characteristics of transformed fibroblastic cells (rounded shape. disordered alignment, and low adhesion to substratum), as well as enhanced agglutinability by plant lectins and ability to grow in agar, were demonstrated in one of four FeLV-infected, FOCMApositive cultures. Findings showed that FOCMA may be expressed in FeLV-infected monolayer cells independent of transformation as assessed by in vitro criteria.
Blood and Water
Authors: Karl E. Sandbank
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Crosby (<b>219</b>:1212, 1971) wrote, "Had Michelangelo really been with it, he would not have put the spear wound at the traditional location above the liver, but knowing that blood and water came from the wound, he would have placed it close to the symphysis pubis." Under Roman law, the sentence of death by crucifixion was executed on the Tau cross—the horizontal beam (patibulum) rested on the vertical stake (stipes). Most crosses were low (humilis), 6 feet 8 inches. Jesus approached the Agony under terrifying conditions. Scourging at the Pillar, pain, skin-avulsions, bleeding, crowning with a cap of thorns, facial contusions, nasal-bone fracture, climbing the 650 yards of the Via Dolorosa, carrying the patibulum (about 150 lb), producing contusions of the right shoulder and back, and injuries from falling. These traumata plus the exquisite pain of the nails in the wrists (not the palms) and the lacerations
From the Agency for Health Care Policy and Research
Authors: J. J. Clinton
Journal: JAMA (1992)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
What happens when the private sector plans hospital services for the NHS
Authors: J. J Owens, C. Aitken, M D Rees, P. A West, R. Pollock, M. Rosen, A. M Pollock, M. Dunnigan, A. Macfarlane
Journal: BMJ (1997)

An analysis of the brain weights of 168 alcoholics showed that the mean brain weight of male alcoholics was less (p less than 0.001) than that of a normal population. Two subgroups of alcoholics were identified. Firstly, those with nutritional brain damage (Wernicke9s encephalopathy, caused by vitamin B1 deficiency) and, secondly, those with brains which appeared "normal" macroscopically and microscopically. Any change in the brain weights of this second group was unlikely to be caused by nutritional damage. Both groups had abnormally low brain weights which suggests that alcohol, the factor common to both groups, is more important than nutritional deficiencies in causing brain damage and a reduction in brain weight.
In Vitro Interaction of 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene and Its Biliary Metabolites With Dietary Fibers&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Gulliver, Wayne P., Kutty, Karunakaran P., Laher, Janet M., Barrowman, James A.
Journal: JNCI Journal of the National Cancer Institute (1983)

Journal Article In Vitro Interaction of 7,12-Dimethylbenz[a]anthracene and Its Biliary Metabolites With Dietary Fibers Get access Wayne P. Gulliver, Wayne P. Gulliver Search for other works by this author on: Oxford Academic PubMed Google Scholar Karunakaran P. Kutty, Karunakaran P. Kutty Search for other works by this author on: Oxford Academic PubMed Google Scholar Janet M. Laher, Janet M. Laher Search for other works by this author on: Oxford Academic PubMed Google Scholar James A. Barrowman James A. Barrowman 5 5Address reprint requests to Dr. Barrowman. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 71, Issue 1, July 1983, Pages 207–210, https://doi.org/10.1093/jnci/71.1.207 Published: 01 July 1983 Article history Received: 17 November 1982 Accepted: 04 March 1983 Published: 01 July 1983
Viruslike Particles in Hamster Embryos, Fetuses, and Tumors<xref ref-type="fn" rid="FN2">2</xref>
Authors: Halina Sobis, M. Vandeputte
Journal: JNCI Journal of the National Cancer Institute (1978)

Intracisternal viruslike particles were present in outbred Syrian golden and inbred ALB/Mey Pfd hamster blastocysts, embryos, and fetuses. Their morphology was identical to that of the “spoked” viruslike particles found in hamster tumors. They were released in great numbers in the embryonal tissues until day 9 of pregnancy and were found until day 13 in the fetal tissues. Thereafter, these viruslike particles were no longer observed in the fetus. They were never recorded in normal adult hamster tissues.
The 'Barely Veiled Warning'
Authors: Michael F. Loudon
Journal: JAMA (1988)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal